X-ray studies of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP.
The X-ray structure of the eukaryotic translation initiation factor 4E (eIF4E), bound to 7-methyl-GDP, has been determined at 2.2A resolution. eIF4E recognizes 5' 7-methyl-G(5')ppp(5')N mRNA caps during the rate-limiting initiation step of translation. The protein resembles a cupped hand, and consists of a curved, 8-stranded antiparallel beta-sheet, backed by three long alpha-helices. 7-methyl-GDP binds in a narrow cap-binding slot on the molecule's concave surface, where 7-methyl-guanine recognition is mediated by base sandwiching between two conserved tryptophans, plus formation of three hydrogen bonds and a van der Waals contact between its N7-methyl group and a third conserved tryptophan. Additional protein-ligand interactions include salt bridges and hydrogen bonds, plus water-mediated hydrogen bonds. The observed mode of 5' m-RNA cap recognition is almost certainly conserved among all known eIF4Es.
Marcotrigiano
J
J
Laboratory of Molecular Biophysics, Rockefeller University, New York, NY 10021, USA.
Gingras
A C
AC
Sonenberg
N
N
Burley
S K
SK
D018360:Crystallography, X-Ray; D015226:Dinucleoside Phosphates / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D010448:Peptide Initiation Factors / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012315:RNA Caps / Q000378:metabolism
D015226:Dinucleoside Phosphates; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D012315:RNA Caps; C111106:7-methylguanosine 5'-diphosphate; D006153:Guanosine Diphosphate; C062229:7-methyl-diguanosine triphosphate